Fucoxanthin regulates macrophage pyroptosis through the PI3K/AKT/mTOR signalling pathway

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Fucoxanthin inhibits macrophage pyroptosis by reducing oxidative stress and inflammatory factor release through the PI3K/AKT/mTOR signaling pathway.

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This study investigated the mechanism by which fucoxanthin modulates macrophage pyroptosis using an in vitro model of M2 macrophages induced by lipopolysaccharide and ATP. The researchers found that fucoxanthin pretreatment significantly reduced oxidative stress, reactive oxygen species release, and the expression of key pyroptotic markers including NLRP3, caspase-1, and GSDMD. These protective effects were mediated through the inhibition of the PI3K/AKT/mTOR signaling pathway, thereby suppressing inflammatory cytokine release such as IL-1β and IL-18. Relevance to endometriosis: listed as one indication for potential therapeutic intervention via macrophage modulation, though the paper's main focus is the molecular mechanism of fucoxanthin on macrophages rather than clinical disease management.

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Abstract

BACKGROUND: Pyroptosis has been reported to occur in several diseases, such as atherosclerosis, nonalcoholic steatohepatitis, and endometriosis. Although fucoxanthin has several biological properties (particularly anti-inflammatory properties), the mechanism through which fucoxanthin modulates or inhibits pyroptosis pathways is unclear. The present study aimed to determine whether fucoxanthin ameliorate endometriosis by preventing macrophage pyroptosis. METHODS AND RESULTS: A model of localized cell death in M2 macrophages induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) was developed. Fucoxanthin decreased the ATP- and LPS-induced pyroptosis of M2 macrophage. Pretreatment with fucoxanthin alleviated oxidative stress and decreased the release of Reactive Oxygen Species (ROS) and LDH from M2 macrophages. Fucoxanthin pretreatment decreased the mRNA expression levels of GSDMD, NLRP3, caspase-1, IL-18, and IL-1β and inhibited the activation of the NLRP3 inflammasome and decreased the protein expression levels of Caspase-1 and GSDMD. In addition, fucoxanthin treatment reduced inflammatory signalling and decreased the expression and release of the IL-18 and IL-1β inflammatory factors. CONCLUSIONS: Fucoxanthin prevents macrophage pyroptosis by inhibiting the mammalian target of rapamycin (mTOR), protein kinase B (AKT), and phosphatidylinositol 3-kinase (PI3K) signalling pathway. CLINICAL TRIAL REGISTRATION: Clinical trial number: not applicable.
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Abstract

Background Pyroptosis has been reported to occur in several diseases, such as atherosclerosis, nonalcoholic steatohepatitis, and endometriosis. Although fucoxanthin has several biological properties (particularly anti-inflammatory properties), the mechanism through which fucoxanthin modulates or inhibits pyroptosis pathways is unclear. The present study aimed to determine whether fucoxanthin ameliorate endometriosis by preventing macrophage pyroptosis.

Methods

and results A model of localized cell death in M2 macrophages induced by lipopolysaccharide (LPS) and adenosine triphosphate (ATP) was developed. Fucoxanthin decreased the ATP- and LPS-induced pyroptosis of M2 macrophage. Pretreatment with fucoxanthin alleviated oxidative stress and decreased the release of Reactive Oxygen Species (ROS) and LDH from M2 macrophages. Fucoxanthin pretreatment decreased the mRNA expression levels of GSDMD, NLRP3, caspase-1, IL-18, and IL-1β and inhibited the activation of the NLRP3 inflammasome and decreased the protein expression levels of Caspase-1 and GSDMD. In addition, fucoxanthin treatment reduced inflammatory signalling and decreased the expression and release of the IL-18 and IL-1β inflammatory factors.

Conclusions

Fucoxanthin prevents macrophage pyroptosis by inhibiting the mammalian target of rapamycin (mTOR), protein kinase B (AKT), and phosphatidylinositol 3-kinase (PI3K) signalling pathway. Clinical Trial Registration Clinical trial number: not applicable Similar content being viewed by others Data availability No datasets were generated or analysed during the current study.

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Acknowledgements

This study was partially supported by the Bengbu Medical University. Funding This work was supported by the Bengbu Medical University Graduate Student Research and Innovation Program Project (Byycx23087). Author information Authors and Affiliations Contributions All authors contributed to the study conception and design. Material preparation was prepared by Taotao Rong. Data collection was performed by Ziwei Pei, Mingjuan Zhang and Lili Lv. The first draft of the manuscript was written by Ziwei Pei. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Ethics approval This article does not contain any studies with human participants or animals performed by any of the authors. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Pei, Z., Zhang, M., Rong, T. et al. Fucoxanthin regulates macrophage pyroptosis through the PI3K/AKT/mTOR signalling pathway. Mol Biol Rep 53, 250 (2026). https://doi.org/10.1007/s11033-025-11408-z Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s11033-025-11408-z

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Condition tags

endometriosis

MeSH descriptors

Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages Macrophages

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References (39)

SciLite annotations

chemicals 11
fucoxanthin fucoxanthin fucoxanthin fucoxanthin lipopolysaccharide adenosine 5'-monophosphate fucoxanthin fucoxanthin oxygen fucoxanthin fucoxanthin

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